In 1930 or 1931, Chambers married the young artist Esther Shemitz (1900–1986).  Shemitz, who had studied at the Art Students League and integrated herself into New York City's intellectual circles, met Chambers at the 1926 textile strike at Passaic, New Jersey. They then underwent a stormy courtship that faced resistance from their comrades, with Chambers having climbed through her window at five o'clock in the morning to propose. Shemitz identified as "a pacifist rather than a revolutionary." In the 1920s, she worked for The World Tomorrow, a pacifist magazine.
The couple had two children, a son, John, and a daughter, Ellen, during the 1930s. Communist leadership had demanded that the family abort the first pregnancy, but Chambers secretly refused. His decision marked a key point in his gradual disillusionment with communism. He regarded the birth of his first child as "the most miraculous thing that had ever happened in my life".
In a letter to J. Edgar Hoover, Chambers wrote that he had numerous homosexual liaisons during the 1930s, starting in 1933. He said that his frequent traveling gave him an opportunity for "cruising", especially in New York City and Washington, D.C. He insisted that he kept these activities secret from everyone, including his communist handlers and his comrades given their negative attitudes towards homosexuality. Chambers also had heterosexual affairs.
Chambers told the FBI that he gave up these practices in 1938 when he left the communist underground. He attributed this change of heart to his newfound Christianity. Chambers' admissions, given the strong social attitudes against homosexuals in 1949, led to a hostile response.